Xenotransplantation of pig islets in diabetic dogs with use of a microcapsule composed of agarose and polystyrene sulfonic acid mixed gel
Xenotransplantation of pig islets in diabetic dogs with use of a microcapsule composed of agarose and polystyrene sulfonic acid mixed gel
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DOI：
10.1097/00006676-200207000-00020
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发表时间：
2002-07-01
期刊：
影响因子：
2.9
通讯作者：
Nakajima, Y
中科院分区：
文献类型：
--
作者：
Kin, T;Iwata, H;Nakajima, Y
简介：作者设计了一种由琼脂糖和聚苯乙烯磺酸（PSSa）混合凝胶组成的微胶囊，可提供抵抗补体攻击的保护屏障。包封在琼脂糖-PSSa微胶囊中的胰岛异种移植物已显示在无免疫抑制的情况下使具有化学诱导的糖尿病的啮齿动物的血糖正常化延长的时间段。目的：探讨琼脂糖-聚苯乙烯-α微囊化软脑膜胰岛在跛行动物模型中逆转糖尿病的疗效。方法：通过全胰腺切除术在比格犬受体中诱导糖尿病。每个受体接受3至5次腹膜内注射包封的（n = 5）或未包封的猪胰岛（n = 2）。结果如下：在接受微囊化胰岛的所有狗中，通过消除或减少外静脉胰岛素需求来确定，移植物功能持续7.4 +/-3.1周（平均标准误差）。在三个受者中，空腹血糖水平维持在小于或等于200 mg/dL，没有任何外源性胰岛素，持续6天，50天和119天。在所有犬的血清中检测到循环猪C-肽的微囊化胰岛移植后。免疫组织学检查显示微囊中存在胰岛素阳性细胞。相比之下，在两只接受非包膜胰岛的狗中，没有移植功能。结论：该初步研究表明，琼脂糖-PSSa微囊化的猪胰岛可以在没有免疫抑制的完全胰腺切除的糖尿病狗中存活数周或数月并发挥功能。
Introduction: The authors have designed a microcapsule composed of agarose and polystyrene sulfonic acid (PSSa) mixed gel that provides a protective barrier against complement attack. Xenografts of islets, encapsulated in an agarose-PSSa microcapsule, have been shown to normalize blood glucose in rodents with chemically induced diabetes for extended periods of time without immunosuppression. Aim: To investigate the efficacy of agarose-PSSa microencapsulated pia islets in reversing diabetes in a lame animal model. Methodology: Diabetes was induced in beagle recipients by total pancreatectomy. Each recipient received three to five intraperitoneal injections of either encapsulated (n = 5) or nonencapsulated pig islets (n = 2). Results: In all dogs receiving microencapsulated islets, the graft function was achieved for 7.4 +/- 3.1 weeks (mean standard error), as determined by elimination or reduction of exoaenous insulin requirement. In three recipients, the fasting blood glucose levels were maintained at less than or equal to200 mg/dL without any exogenous insulin for a period of 6, 50, and 119 days. Circulating porcine C-peptide was detected in the sera of all dogs after transplantation of encapsulated islets. Immunohistologic examination revealed the presence of insulin-positive cells in the microcapsules. In contrast, in two dogs receiving nonencapsulated islets there was no graft function. Conclusions: This preliminary study demonstrates that agarose-PSSa microencapsulated pig islets can survive and function for weeks or months in totally pancreatectomized diabetic dogs without immunosuppression.